Parotid tumors: fine-needle aspiration and/or frozen section

OBJECTIVE: The purpose of this study was to analyze and compare the value of fine-needle aspiration cytology (FNAC) and frozen section (FS) analysis in the assessment of parotid gland tumors. STUDY DESIGN: Chart review and cross-sectional analysis. SUBJECTS AND METHODS: FNAC and FS analysis of 110 parotid tumors, 68 malignancies and 42 benign tumors, were analyzed and compared with the final histopathologic diagnosis. RESULTS: The accuracy, sensitivity, and specificity of FNAC in detecting malignant tumors were 79 percent, 74 percent, and 88 percent, respectively. On FS analysis, the accuracy, sensitivity, and specificity in detecting malignant tumors were 94 percent, 93 percent, and 95 percent, respectively. The histologic tumor type was correctly diagnosed by FNAC and FS in 27 of 42 (64%) and 39 of 42 (93%) benign tumors, respectively, and in 24 of 68 (35%) and 49 of 68 (72%) malignant neoplasms, respectively. CONCLUSION: The current analysis showed a superiority of FS compared with FNAC regarding the diagnosis of malignancy and tumor typing. FNAC alone is not prone to determine the surgical management of parotid malignancies.

Deletion of CD39 inhibits development of metastatic liver cancer

New vessel formation and tumor infiltrating lymphocytes (TIL) influence host responses to malignant tissues. Extracellular adenosine-mediated pathways promote both vascular endothelial cell proliferation and inhibit cytotoxic T cells, thereby potentiating cancer growth. CD39 is the dominant ectonucleotidase of vascular and T regulatory cells and has the potential to generate high levels of adenosine locally. We have previously shown that deletion of Cd39 results in angiogenic failure and T regulatory cell dysfunction with loss of immune suppressive functions. Aim: Investigate impact of CD39 upon development of hepatic metastases. Methods and Results: We studied the development of metastatic liver deposits following portal vein infusion of 1.5x105 melanoma B16/F10 cells, with luciferase expression, in wild type and Cd39-null C57BL/6 mice (n=24). Tumor formation in liver was directly examined and animals imaged at days 7-17 after tumor cell implantation. As predicted, the formation of hepatic malignant foci was markedly suppressed in Cd39-null mice, at all time points examined. To test whether the major impact of Cd39-deletion was upon neovasculature formation or immune responsiveness, adoptive transfer experiments were conducted. Bone marrow transplants (BMT) from Cd39-null or wild type BL/6 mice were placed in lethally irradiated control and/or null mice, in a crossover manner (total n=24 for each group, respectively). Eight weeks postadoptive transfer, melanoma cells were infused via portal vein as before and tumor growth studied. The Cd39-null mice that received wild type BMT mirrored the wild type phenotype with progressive tumor growth observed (n=8 per time point; p=0.015). In contrast, metastases were significantly inhibited in both number and size and ultimately became necrotic in the wild type mice that had received Cd39-null BMT. Conclusions: Bone marrow derived cells mediate the major inhibitory effects of CD39 deletion on tumor growth. Pharmacological inhibition of CD39 may find utility as an adjunct therapy in the management of hepatic malignancy.

[Diagnosis, treatment and follow up of prostata cancer]

Prostate cancer is the most frequent diagnosed malignancy in men with an increasing incidence. In well informed men between the age of 50 and 70 years screening should be offered when requested. Not every newly diagnosed prostate cancer requires immediate treatment. Curative treatment should be offered to men with a minimal life expectancy of 10 years. In men older than 50-75 years, therefore further screening is not necessary due to a lack of a therapeutic consequence. Curative treatment options enclose as the gold standard surgical removal, i.e. open radical prostatectomy with pelvic lymph node dissection, and radio-oncologic treatments, be it percutaneous radiation therapy, brachytherapies or a combination thereof. Palliative treatment options are mainly hormonal treatment (medical or surgical androgen deprivation), local radiation, treatment with bisphosphonates, chemotherapy and surgical desobstruction of the prostate. Regular follow up allows for early detection of recurrences and an active treatment concept.

Evaluation of 15 mandibular reconstructions with Dumbach Titan Mesh-System and particulate cancellous bone and marrow harvested from bilateral posterior ilia

This study reports on 15 mandibular reconstructions using the Dumbach Titan Mesh-System and particulate cancellous bone and marrow harvested from bilateral posterior ilia. All cases showed segmental defects. Eleven cases involved patients with malignant tumor. Six patients had received irradiation of 40-50 Gy. Reconstructions were performed immediately in 1 patient and secondarily in the remaining 14 patients. In 13 cases, mandibles were successfully reconstructed. Of these 13 patients, 9 reconstructions were completed without complications, whereas the other 4 cases showed complications. In 2 cases, reconstruction failed completely. Overall success rate was 87%. Statistical analysis revealed the extent of mandibular defect, but not malignancy of the original disease or radiotherapy of

Bulky extramedullary hematopoiesis is not a rare complication of congenital dyserythropoietic anemia

Bulky extramedullary hematopoiesis, usually detected in the thorax by imaging techniques, is a well-known complication in many types of congenital anemias. Here, we describe 12 cases of congenital dyserythropoietic anemia with extramedullary hematopoiesis which was always located in the paravertebral space of the thoracic spine and in other paraspinal regions in a few cases. All bulks were originally detected in chest radiographs and confirmed by imaging techniques such as computed tomography and/or magnetic resonance imaging. In some cases, thoracotomy was performed for suspected malignancy. Although the true prevalence is not known, paravertebral masses in patients with CDA of any type are not uncommon and should be the first differential diagnosis considered when masses adjacent to the spine are detected in this disorder.

High-risk clinical stage I nonseminomatous germ cell tumors: the case for chemotherapy

Testis cancer is the most frequent solid malignancy in young men. The majority of patients present with clinical stage I disease and about 50% of them are nonseminomatous germ cell tumors. In this initial stage of disease there is a subgroup of patients at high risk with a likelihood of more than 50% for relapse. Treatment options for these patients include: retroperitoneal lymph node dissection (RPLND), albeit 6-10% of patients will relapse outside the field of RPLND, active surveillance with even higher relapse rates and adjuvant chemotherapy. As most of these patients have the chance to become long-term survivors, avoidance of long-term side effects is of utmost importance. This review provides information on the potential of chemotherapy to achieve a higher chance of cure for patients with high-risk clinical stage I disease than its therapeutic alternatives and addresses toxicity and dose dependency.

Long-term follow up (37-69 years) of patients with bladder exstrophy treated with ureterosigmoidostomy: uro-nephrological outcome

OBJECTIVE: To describe the urological and nephrological long-term outcome of patients born with classical bladder exstrophy treated with bilateral ureterosigmoidostomies in early childhood. PATIENTS AND METHOD: Out of 42 patients born with bladder exstrophy in Switzerland between 1937 and 1968, 25 participated in this study; seven had died, seven were lost to follow up and three refused consent. Assessment included chart review, clinical examination, and assessment of renal function and morphology. RESULTS: After a follow-up period of 37-69 years ((mean 50 years), 13 of the 25 participants (52%) had their ureterosigmoidostomy still in place. All others had different forms of urinary diversions. Fifteen (60%) patients had normal renal function or mild chronic kidney disease as assessed by estimated glomerular filtration rate. Three patients were on renal replacement therapy. MRI (n=16) showed 10 morphologically normal kidneys. One patient suffered from adenocarcinoma of the colon, five had benign colonic polyps, one urethral papillary carcinoma and 18 no evidence of tumor. CONCLUSION: The majority of our patients have normal or mildly impaired renal function and a well functioning ureterosigmoidostomy. This is remarkable, given the fact that ureterosigmoidostomies are considered to be refluxing high-pressure reservoirs at risk of renal injury and malignancy.

Regular follow-up after curative resection of nonsmall cell lung cancer: a real benefit for patients?

Even though complete resection is regarded as the only curative treatment for nonsmall cell lung cancer (NSCLC), >50% of resected patients die from a recurrence or a second primary tumour of the lung within 5 yrs. It remains unclear, whether follow-up in these patients is cost-effective and whether it can improve the outcome due to early detection of recurrent tumour. The benefit of regular follow-up in a consecutive series of 563 patients, who had undergone potentially curative resection for NSCLC at the University Hospital, was analysed. The follow-up consisted of clinical visits and chest radiography according to a standard protocol for up to 10 yrs. Survival rates were estimated using the Kaplan-Meier analysis method and the cost-effectiveness of the follow-up programme was assessed. A total of 23 patients (6.4% of the group with lobectomy) underwent further operation with curative intent for a second pulmonary malignancy. The regular follow-up over a 10-yr period provided the chance for a second curative treatment to 3.8% of all patients. The calculated costs per life-yr gained were 90,000 Swiss Francs. The cost-effectiveness of the follow-up protocol was far above those of comparable large-scale surveillance programmes. Based on these data, the intensity and duration of the follow-up was reduced.

Diagnostic approach to hypercalcemia: relevance of parathyroid hormone and parathyroid hormone-related protein measurements

Background: Parathyroid hormone (PTH) and parathyroid hormone-related protein (PTH-rP) are two potent hypercalcemic hormones that act on the same targets. Autonomous secretion of the former is involved in primary hyperparathyroidism (PHPT), whereas the latter is responsible for humoral hypercalcemia of malignancy (HHM). Methods: From 250 consecutive, hypercalcemic serum samples sent to our laboratory for assessment of intact PTH, we were able to obtain clinical information, as well as an additional plasma sample for PTH-rP measurement, in 134 patients. At the time of sampling, patients could be classified into seven groups: cancer without known bone metastases (CaNoMeta, n=36), cancer with bone metastases (CaMeta, n=9), no evidence of cancer (noEvCa, n=71), sarcoidosis (Sarc, n=3), end-stage renal disease (ESRD, n=12), vitamin D overdose (VIT-D, n=2), and hyperthyroidism (Thyr, n=1). Results: In the CaNoMeta group, 29/36 patients had elevated PTH-rP levels, 9/36 patients had inappropriately elevated PTH levels, and 5/36 had elevated levels of both hormones. In the CaMeta group, three of the nine patients had inappropriately elevated PTH levels, two of them with concomitantly elevated PTH-rP levels. In the NoEvCa group, 63/71 patients had an inappropriate elevation of PTH levels and were diagnosed as having PHPT. Four of the 71 patients had elevated levels of both PTH and PTH-rP; three of them were in poor health and died within a short period of time. All of the ESRD patients had very high PTH and normal PTH-rP levels, except for one woman with high PTH-rP and undetectable PTH levels; she died from what later turned out to be a recurrent bladder carcinoma. In the Sarc, Vit-D, and Thyr groups, both PTH and PTH-rP levels were normal. Conclusions: (1) Elevated PTH-rP levels are a common finding in cancer patients without bone metastases. Intact PTH, however, should always be measured in hypercalcemic patients with malignancy because concurrent primary hyperparathyroidism is not rare. (2) Primary hyperparathyroidism accounts for hypercalcemia in 90% of patients without evidence of cancer whose PTH-rP levels may also be found to be elevated in a few cases, even some with surgically demonstrated parathyroid adenoma.

Cerebral extension of steroid-responsive meningitis arteritis in a boxer

A comatose 30-month-old, entire male boxer was presented because of an acute history of a cluster of three to four seizures. Neurological examination suggested a diffuse to multifocal intracranial lesion. Magnetic resonance tomography revealed symmetrical multifocal to diffuse changes of the cerebral grey matter and ependymal lining with sediment in the lateral ventricles. Haematological examination revealed leucocytosis with neutrophilia. Cerebrospinal fluid examination revealed high protein concentration and polymorphonuclear pleocytosis. Despite antiepileptic treatment, therapy against increased intracranial pressure and antibiosis, the dog's condition continued to deteriorate and he was euthanased. Pathological examination revealed fibrinosuppurative meningo-ependymitis and necrotising arteritis throughout the brain. In addition, chronic inflammation and arterial stenosis was found in the spinal meninges. No infectious agent was found. A diagnosis of steroid-responsive meningitis arteritis was made. The massive extension into the meninges and ventricular system of the forebrain has not been described previously in dogs with steroid-responsive meningitis arteritis and should be considered in the differential diagnosis when an intracranial suppurative infection is suspected.

Incident malignancies among older long-term breast cancer survivors and an age-matched and site-matched nonbreast cancer comparison group over 10 years of follow-up

BACKGROUND Of the approximately 2.4 million American women with a history of breast cancer, 43% are aged ≥ 65 years and are at risk for developing subsequent malignancies. METHODS Women from 6 geographically diverse sites included 5-year breast cancer survivors (N = 1361) who were diagnosed between 1990 and 1994 at age ≥ 65 years with stage I or II disease and a comparison group of women without breast cancer (N = 1361). Women in the comparison group were age-matched and site-matched to breast cancer survivors on the date of breast cancer diagnosis. Follow-up began 5 years after the index date (survivor diagnosis date or comparison enrollment date) until death, disenrollment, or through 15 years after the index date. Data were collected from medical records and electronic sources (cancer registry, administrative, clinical, National Death Index). Analyses included descriptive statistics, crude incidence rates, and Cox proportional hazards regression models for estimating the risk of incident malignancy and were adjusted for death as a competing risk. RESULTS Survivors and women in the comparison group were similar: >82% were white, 55% had a Charlson Comorbidity Index of 0, and ≥ 73% had a body mass index ≤ 30 kg/m(2) . Of all 306 women (N = 160 in the survivor group, N = 146 in the comparison group) who developed a first incident malignancy during follow-up, the mean time to malignancy was similar (4.37 ± 2.81 years vs 4.03 ± 2.76 years, respectively; P = .28), whereas unadjusted incidence rates were slightly higher in survivors (1882 vs 1620 per 100,000 person years). The adjusted hazard of developing a first incident malignancy was slightly elevated in survivors in relation to women in the comparison group, but it was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.94-1.47). CONCLUSIONS Older women who survived 5 years after an early stage breast cancer diagnosis were not at an elevated risk for developing subsequent incident malignancies up to 15 years after their breast cancer diagnosis.

Epoetin and Darbepoetin for Managing Anemia in Patients Undergoing Cancer Treatment: Comparative Effectiveness Update

Objectives: To update the 2006 systematic review of the comparative benefits and harms of erythropoiesis-stimulating agent (ESA) strategies and non-ESA strategies to manage anemia in patients undergoing chemotherapy and/or radiation for malignancy (excluding myelodysplastic syndrome and acute leukemia), including the impact of alternative thresholds for initiating treatment and optimal duration of therapy. Data sources: Literature searches were updated in electronic databases (n=3), conference proceedings (n=3), and Food and Drug Administration transcripts. Multiple sources (n=13) were searched for potential gray literature. A primary source for current survival evidence was a recently published individual patient data meta-analysis. In that meta-analysis, patient data were obtained from investigators for studies enrolling more than 50 patients per arm. Because those data constitute the most currently available data for this update, as well as the source for on-study (active treatment) mortality data, we limited inclusion in the current report to studies enrolling more than 50 patients per arm to avoid potential differential endpoint ascertainment in smaller studies. Review methods: Title and abstract screening was performed by one or two (to resolve uncertainty) reviewers; potentially included publications were reviewed in full text. Two or three (to resolve disagreements) reviewers assessed trial quality. Results were independently verified and pooled for outcomes of interest. The balance of benefits and harms was examined in a decision model. Results: We evaluated evidence from 5 trials directly comparing darbepoetin with epoetin, 41 trials comparing epoetin with control, and 8 trials comparing darbepoetin with control; 5 trials evaluated early versus late (delay until Hb ≤9 to 11 g/dL) treatment. Trials varied according to duration, tumor types, cancer therapy, trial quality, iron supplementation, baseline hemoglobin, ESA dosing frequency (and therefore amount per dose), and dose escalation. ESAs decreased the risk of transfusion (pooled relative risk [RR], 0.58; 95% confidence interval [CI], 0.53 to 0.64; I2 = 51%; 38 trials) without evidence of meaningful difference between epoetin and darbepoetin. Thromboembolic event rates were higher in ESA-treated patients (pooled RR, 1.51; 95% CI, 1.30 to 1.74; I2 = 0%; 37 trials) without difference between epoetin and darbepoetin. In 14 trials reporting the Functional Assessment of Cancer Therapy (FACT)-Fatigue subscale, the most common patient-reported outcome, scores decreased by −0.6 in control arms (95% CI, −6.4 to 5.2; I2 = 0%) and increased by 2.1 in ESA arms (95% CI, −3.9 to 8.1; I2 = 0%). There were fewer thromboembolic and on-study mortality adverse events when ESA treatment was delayed until baseline Hb was less than 10 g/dL, in keeping with current treatment practice, but the difference in effect from early treatment was not significant, and the evidence was limited and insufficient for conclusions. No evidence informed optimal duration of therapy. Mortality was increased during the on-study period (pooled hazard ratio [HR], 1.17; 95% CI, 1.04 to 1.31; I2 = 0%; 37 trials). There was one additional death for every 59 treated patients when the control arm on-study mortality was 10 percent and one additional death for every 588 treated patients when the control-arm on-study mortality was 1 percent. A cohort decision model yielded a consistent result—greater loss of life-years when control arm on-study mortality was higher. There was no discernible increase in mortality with ESA use over the longest available followup (pooled HR, 1.04; 95% CI, 0.99 to 1.10; I2 = 38%; 44 trials), but many trials did not include an overall survival endpoint and potential time-dependent confounding was not considered. Conclusions: Results of this update were consistent with the 2006 review. ESAs reduced the need for transfusions and increased the risk of thromboembolism. FACT-Fatigue scores were better with ESA use but the magnitude was less than the minimal clinically important difference. An increase in mortality accompanied the use of ESAs. An important unanswered question is whether dosing practices and overall ESA exposure might influence harms.

TH2 cytokines from malignant cells suppress TH1 responses and enforce a global TH2 bias in leukemic cutaneous T-cell lymphoma

PURPOSE In leukemic cutaneous T-cell lymphoma (L-CTCL), malignant T cells accumulate in the blood and give rise to widespread skin inflammation. Patients have intense pruritus, increased immunoglobulin E (IgE), and decreased T-helper (TH)-1 responses, and most die from infection. Depleting malignant T cells while preserving normal immunity is a clinical challenge. L-CTCL has been variably described as a malignancy of regulatory, TH2 and TH17 cells. EXPERIMENTAL DESIGN We analyzed phenotype and cytokine production in malignant and benign L-CTCL T cells, characterized the effects of malignant T cells on healthy T cells, and studied the immunomodulatory effects of treatment modalities in patients with L-CTCL. RESULTS Twelve out of 12 patients with L-CTCL overproduced TH2 cytokines. Remaining benign T cells were also strongly TH2 biased, suggesting a global TH2 skewing of the T-cell repertoire. Culture of benign T cells away from the malignant clone reduced TH2 and enhanced TH1 responses, but separate culture had no effect on malignant T cells. Coculture of healthy T cells with L-CTCL T cells reduced IFNγ production and neutralizing antibodies to interleukin (IL)-4 and IL-13 restored TH1 responses. In patients, enhanced TH1 responses were observed following a variety of treatment modalities that reduced malignant T-cell burden. CONCLUSIONS A global TH2 bias exists in both benign and malignant T cells in L-CTCL and may underlie the infectious susceptibility of patients. TH2 cytokines from malignant cells strongly inhibited TH1 responses. Our results suggest that therapies that inhibit TH2 cytokine activity, by virtue of their ability to improve TH1 responses, may have the potential to enhance both anticancer and antipathogen responses.

Overview of dermatologic problems following liver transplantation

Liver transplantation recipients, like other solid organ transplantation recipients, have an increased risk of dermatologic problems due to their long-term immunosuppression and benefit from pre-and post-transplantation screenings, and management by a dermatologist and dermatologic care should be integrated into the comprehensive, multidisciplinary care of liver transplantation recipients [1,2]. Cutaneous findings include aesthetic alterations, infections, precancerous lesions, and malignancies. The severity of skin alterations ranges from benign, unpleasant changes to life-threatening conditions [3-5]. In addition to skin cancer diagnosis and management, visits with a dermatologist serve to educate and improve the patient's sun-protection behavior. Among all solid organ transplantations, liver transplantation requires the least amount of immunosuppression, sometimes even permitting its complete cessation [6]. As a result, patients who have undergone liver transplantation tend to have fewer dermatologic complications compared with other solid organ transplantation recipients [7]. However, due to the large volume of the liver, patients undergoing liver transplantation receive more donor lymphocytes than kidney, heart, or lung transplantation recipients. Because of the immunosuppression, the transplanted lymphocytes proliferate and rarely trigger graft-versus-host-disease [8,9]. This topic will provide an overview of dermatologic disorders that may be seen following liver transplantation. A detailed discussion of skin cancer following solid organ transplantation and the general management of patients following liver transplantation are discussed separately. (See "Development of malignancy following solid organ transplantation" and "Management of skin cancer in solid organ transplant recipients" and "Long-term management of adult liver transplant recipients".)

Cerebral High-grade Oligodendroglioma with Sarcomatous Transdifferentiation ("Oligosarcoma") in a Boxer Dog.

A 9-year-old Boxer dog was referred to the Veterinary Teaching Hospital of the University of Bern for a history of chronic neck pain and gait problems, which rapidly progressed to a non-ambulatory status. Magnetic resonance imaging (MRI) examination of the head revealed a large intra-axial space-occupying lesion that was divided in two portions interconnected by a thin isthmus at the level of the cerebellar tentorium. Histopathology revealed a biphasic malignant neoplasm composed of neuroepithelial and mesenchymal elements. The former displayed characteristics of conventional anaplastic oligodendroglioma involving brisk mitotic activity and glomeruloid microvascular proliferation on a background of a fibrillary round cells with "honeycomb-like" perinuclear vacuolation. Conversely, the sarcomatous moiety exhibited haphazard fascicles of spindle cells amidst an intricate mesh of pericellular basal lamina and broad bands of collagen. Both tumor cell populations immunoreacted for Olig-2 and – to a lesser extent – GFAP. In addition, the sarcomatous areas focally expressed vimentin, muscular actin, and smooth muscle actin. "Oligosarcoma" - an exquisitely uncommon pattern of oligodendroglial malignancy in humans - has not previously been reported to affect dogs, although oligodendroglioma is a common CNS tumor in this species. Whether canine oligosarcoma shares with its human counterpart not only morphological aspects, but also molecular signatures, clinical behavior and responsiveness to therapy merits further investigation. In humans, oligodendroglial differentiation tends to confer significant clinical advantage with respect to prognosis and adjuvant treatment options. The awareness of such hallmarks and the investigation of their impact on prognosis are crucial for improved therapeutical strategies in dogs.